Narendra and Youle review the current understanding of the role of PINK1–Parkin in the quality control of mitophagy, highlighting the underlying mechanisms and physiological relevance of the pathway, as well as its role in neuroprotection.

Pluripotent stem cells are being used to generate models of early embryogenesis that are promising for discovery and translational research. To be useful, these models require critical consideration of their level of efficiency and fidelity to natural embryos. Here we propose criteria with which to raise the standards of stem-cell-based embryo models of human embryogenesis.

Man and Kanneganti discuss how pattern-recognition sensors in innate immune cells recognize and respond to cell-death signatures, and highlight molecular targets for potential therapeutic development.

With biomedical sciences quickly outgrowing many other application areas in terms of data generation, there is a unique opportunity for life sciences to become one of the greatest beneficiaries of research in machine learning and AI, and also inspire foundational developments in it.

Fernandes, Angelidaki et al. provide evidence supporting the spatial separation of mTORC1 activation and signalling. Differentially localized mTORC1 complexes phosphorylate distinct substrates in response to different amino acid supplies.

Dardano et al. generate human pluripotent stem cell-derived cardiac organoids capable of undergoing endothelial-to-haematopoietic transition and producing haematopoietic cells.

Stockhammer, Adarska et al. describe ARF1 compartments as the site of adaptor- and clathrin-dependent post-Golgi sorting. Shedding of ARF1 and maturation into recycling endosomes drives sorting of secretory and endocytic recycling cargo.

Toettcher, McNamara and colleagues use synthetic ‘signal-recording’ gene circuits on mouse gastruloids and find that cell sorting rearranges patchy domains of Wnt activity into a single pole, which defines the gastruloid anterior–posterior axis.

Bose, Rankovic et al. show that a specific RNA–RNA kissing-loop interaction plays a crucial role in driving biomolecular condensation of ribonucleoprotein granules in the Drosophila germline.

Zhao et al. report that the Z compartment protein HERD-1 regulates transgenerational epigenetic inheritance in Caenorhabditis elegans at least in part by preventing the mixing of germ granule condensates.